Department of Chemistry, American University of Cairo, Cairo, Egypt.
Institute of Biomedical Engineering, University of Toronto, Toronto, Canada.
Biomed Microdevices. 2021 Feb 2;23(1):10. doi: 10.1007/s10544-021-00544-5.
The advancement of sample preparation techniques is essential for the field of cell-based therapeutics. To obtain cells suited for clinical applications, the entire process starting from acquiring donor tissue biopsy, all through cell transplantation into the recipient, should occur in an integrated, safe, and efficient system. The current laboratory approach for solid tissue-to-cell isolation is invasive and involves multiple incoherent manual procedures running in an open operator-dependent system. Such an approach provides a chain of events for systematic cell loss that would be unfavorable for rare cell populations such as adult and cancer stem cells. A few lab-on-chip platforms were proposed to process biological tissues, however, they were limited to partial tissue dissociation and required additional processing off-chip. Here, we report the first microfluidic platform that can dissociate native biological tissue into ready-to-use single cells. The platform can merge the successive steps of tissue dissociation, debris filtration, cell sieving, washing, and staining in one streamlined process. Performance of the platform was tested with diverse biological tissues and it could yield viable cells that were ready for on or off-chip cell culture without further processing. Microfluidic tissue dissociation using this platform produced a higher number of viable single cells (an average of 2262 cells/ml per milligram of tissue compared to 1233.25 cells/ml/mg with conventional dissociation).
样品制备技术的进步对于细胞治疗领域至关重要。为了获得适合临床应用的细胞，从获取供体组织活检开始，直到将细胞移植到受体中，整个过程都应在一个集成、安全和有效的系统中进行。目前用于固体组织到细胞分离的实验室方法具有侵入性，涉及多个在开放的操作员依赖系统中运行的不连贯的手动过程。这种方法为系统细胞丢失提供了一系列事件，这对于罕见的细胞群体（如成人和癌症干细胞）是不利的。已经提出了一些芯片实验室平台来处理生物组织，但是，它们仅限于部分组织解离，并且需要在芯片外进行额外的处理。在这里，我们报告了第一个可以将天然生物组织解离成即用型单细胞的微流控平台。该平台可以将组织解离、碎片过滤、细胞筛分、洗涤和染色的连续步骤合并到一个简化的过程中。该平台的性能已经通过各种生物组织进行了测试，并且可以产生可用于芯片上或芯片下细胞培养的存活细胞，而无需进一步处理。使用该平台进行微流体组织解离可产生更多的活单细胞（与传统解离相比，每毫克组织平均产生 2262 个细胞/ml，而每毫克组织产生 1233.25 个细胞/ml）。
